ABSTRACT
Cage-type structures based on coordination and dynamic covalent chemistry have the characteristics of facile and efficient preparation but poor stability. Chemically stable organic cages, generally involving fragment coupling and multi-step reactions, are relatively difficult to synthesize. Herein, we offer a general and modular strategy to customize covalent organic cages with diverse skeletons and sizes. First, one skeleton (S) module with three extension (E) modules and three reaction (R) modules are connected by one- or two-step coupling to get the triangular monomer bearing three reaction sites. Then one-pot Friedel-Crafts condensation of the monomer and linking module of paraformaldehyde produces the designed organic cages. The cage forming could be regulated by the geometrical configuration of monomeric blocks. The S-E-R angles in the monomer is crucial; only 120o (2,4-dimethoxyphen as reaction module) or 60o (2,5-dimethoxyphen as reaction module) angle between S-E-R successfully affords the resulting cages. By the rational design of the three modules, a series of organic cages have been constructed. In addition, the host-guest properties show that the representative cages could strongly encapsulate neutral aromatic diimine guests driven by solvophobic interactions in polar solvents, giving the highest association constant of (2.58 ± 0.18) × 105 M-1.
ABSTRACT
Since bacteria in biofilms are inherently resistant to antibiotics and biofilm-associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium-functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti-biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram-positive S.â aureus and Gram-negative E.â coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×104 â M-1 for CFZ/WBP4 and (4.98±0.49)×103 â M-1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E.â coli-infected mice models, providing a novel supramolecular strategy for combating biofilm-associated infections.
Subject(s)
Escherichia coli , Staphylococcus aureus , Mice , Animals , Anti-Bacterial Agents/pharmacology , Biofilms , Cefazolin , Microbial Sensitivity TestsABSTRACT
A series of structurally unusual spirobenzoxazine chromeno[4,3-b]pyrrole derivatives have been efficiently constructed in a single operation from readily available starting materials. This domino transformation forms successively three new rings and provides a fast and economic strategy with excellent diastereoselectivity.
Subject(s)
Pyrroles , Molecular Structure , StereoisomerismABSTRACT
Organic cages are fascinating because of their well-defined 3D cavities, excellent stability, and accessible post-modification. However, the synthesis is normally realized by fragment coupling approach in low yields. Herein, we report one-pot, gram-scale and shape-controlled synthesis of two covalent organic cages (box-shaped [4]cage and triangular prism-shaped [2]cage) in yields of 46 % and 52 %, involving direct condensation of triangular 1,3,5-tris(2,4-dimethoxyphenyl)benzene monomer with paraformaldehyde and isobutyraldehyde, respectively. The cages can convert into high-yielding per-hydroxylated analogues. The [2]cage can be utilized as gas chromatographic stationary phase for high-resolution separation of benzene/cyclohexane and toluene/methylcyclohexane. By changing the central moiety of the triangular monomer and/or aldehyde, this synthetic method would have the potential to be a general strategy to access diverse cages with tunable shape, size, and electronic properties.
ABSTRACT
Traditional macrocyclic hosts have finite cavity sizes, generally 5-10â Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (Ka ) of (4.20±0.23)×104 â M-1 for PXG/WQP3 and (2.46±0.44)×105 â M-1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.
Subject(s)
Antimicrobial Cationic Peptides/chemistry , Calixarenes/chemistry , Macrocyclic Compounds/chemistry , Calixarenes/chemical synthesis , Macrocyclic Compounds/chemical synthesis , Molecular Structure , Protein StabilityABSTRACT
Conformational exchanges of synthetic macrocyclic acceptors are rather fast, which is rarely studied in the absence of guests. Here, we report multiple stimuli-responsive conformational exchanges between two preexisting conformations of 2,2',4,4'-tetramethoxyl biphen[3]arene (MeBP3) macrocycle. Structures of these two conformations are both observed in solid state, and characterized by 1H NMR, 13C NMR and 2D NMR in solution. In particular, conformational exchanges can respond to solvents, temperatures, guest binding and acid/base addition. The current system may have a role to play in the construction of molecular switches and other stimuli-responsive systems.
Subject(s)
Macrocyclic Compounds/chemistry , Models, Molecular , Molecular Conformation , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular Structure , Solvents , TemperatureABSTRACT
Catenated cages represent chemistry's challenging synthetic targets because a three-dimensional assembly is necessary for their formation. Herein, a cyclic bis[2]catenane is constructed through the coordination-driven self-assembly of the interlocked bis-metallacage, by the 90° Pt(II) heteroligation of the endo-functionalized double-bridged tweezer bearing pyridyl moieties and the tetra-carboxylated linker. NMR spectrometry, X-ray crystallography and mass spectrometry confirm the formation of a cyclic bis[2]catenane with "∞"-shaped topology via a 14-component self-assembly. Particularly, reversibly responsive transformation between the bis[2]catenane and the bis-metallacage can be realized by guest exchange, concentration effect and solvent effect. This work represents a novel example of a cyclic cage-based [2]catenane oligomer.
ABSTRACT
Palladium-catalyzed cascade reactions of enynones and isocyanides have been disclosed. This strategy allows for the synthesis of structurally unusual furan-incorporated ketenimines, which are stable and can undergo a formal [4+1] annulation with another isocyanide to yield indenone derivatives.
ABSTRACT
Phosphine-mediated cascade annulations of allenyl ketone and isocyanide have been disclosed. Two molecular allenyl ketones work as different four-carbon synthons to form two rings, respectively, and thus enables the efficient synthesis of a furan-fused eight-membered ring and a spirocycle.
ABSTRACT
Polyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host-guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N3)EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin αvß3-overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 105-106 M-1. We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Polyamines/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Biosynthetic Pathways/drug effects , Breast Neoplasms/pathology , Calixarenes/chemistry , Calixarenes/pharmacology , Calixarenes/therapeutic use , Cations/chemistry , Cations/metabolism , Female , Humans , Integrin alphaVbeta3/metabolism , MCF-7 Cells , Mice , Mice, Nude , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Peptides, Cyclic/therapeutic use , Polyamines/chemistry , Xenograft Model Antitumor AssaysABSTRACT
A novel bicyclization reaction of two molecular allenyl ketones and isocyanides has been disclosed. This strategy allows for the construction of structurally complex spirocyclic lactam-lactone systems in an efficient manner. This protocol also demonstrates other advantages such as high synthetic efficiency, atom economy, and broad substrate scope under mild conditions.
ABSTRACT
Reported here is the highly efficient separation of industrially important cis- and trans-1,2-dichloroethene (cis-DCE and trans-DCE) isomers by activated crystalline 2,2',4,4'-tetramethoxyl biphen[3]arene (MeBP3) materials, MeBP3α. MeBP3 can be synthesized in excellent yield (99 %), and a cyclic pentamer is also obtained when using 1,2-dichloroethane as the solvent. The structure of MeBP3 in the CH3 CN@MeBP3 crystal displays a triangle-shape topology, forming 1D channels through window-to-window packing. Desolvated crystalline MeBP3 materials, MeBP3α, preferentially adsorb cis-DCE vapors over its trans isomer. MeBP3α is able to separate cis-DCE from a 50:50 (v/v) cis/trans-isomer mixture, yielding cis-DCE with a purity of 96.4 % in a single adsorption cycle. Single-crystal structures and powder X-ray diffraction patterns indicate that the uptake of cis-DCE triggers a solid-state structural transformation of MeBP3, suggesting the adaptivity of MeBP3α materials during the sorption process. Moreover, the separation can be performed over multiple cycles without loss of separation selectivity and capacity.
ABSTRACT
Despite progress in the unidirectional complexation of cyclodextrins and calixarenes with nonsymmetric guests, unidirectional complexation using pillararenes as hosts remains scarcely explored. In this report, we describe the formation of unidirectional [2]pseudorotaxane-like complexes which were realized using n-alkyl alcohol guests and pillar[4]arene[1]benzoquinoneoxime made from pillar[4]arene[1]quinone in a selective monofunctionalizing manner.
ABSTRACT
A visible-light-induced oxidative cyclization of N-propargyl anilines with sulfinic acids was developed under external photocatalyst-free conditions. The reaction provides a straightforward route to 3-sulfonated quinoline derivatives with good functional group tolerance, excellent yields and high regio-selectivity.
ABSTRACT
Herein, two new classes of macrocyclic compounds, terphen[n]arenes (TPns) (n=3-6) and quaterphen[n]arenes (QPns) (n=3-6), were designed and synthesized by a one-step condensation reaction in relatively high yields. They comprise 2,2''-dimethoxy terphenyl and 2,2'''-dimethoxy quaterphenyl monomers, respectively, linked by methylene bridges. Given their long and rigid monomers, TPns and QPns have much larger cavities and better self-assembly properties than classic macrocycles. More interestingly, the cyclic pentamers and hexamers TP5, TP6, QP5, and QP6 formed supramolecular organogels, which were composed of interwoven fibers, nanosheets, or entangled macropore networks formed by multiple face-to-face and edge-to-face πâ â â π stacking interactions. The xerogel materials effectively captured volatile iodine, not only in aqueous media but also in the gaseous state, and could be recycled multiple times without obvious loss in performance.
ABSTRACT
A DABCO-catalyzed annulation reaction of pyridin-2-amine and substituted allenoates has been disclosed. This strategy allows for the ring-opening of a pyridine ring system and the formation of two new rings including a pyrimidinone ring and a benzene ring in an efficient manner.
ABSTRACT
A new strategy for supramolecular polymerization is designed and presented, which is based on the wheel-stopper charge-transfer (CT) interactions of [2]rotaxanes containing π-electron-rich pillar[5]arene wheels and electron-deficient pyromellitic diimide (PDI) stoppers.
ABSTRACT
An unusual cascade reaction of isocyanide and enynone using Yb/Ag cooperative catalysis as a key step has been disclosed. The present strategy enables the double isocyanide insertion and subsequent 5-endo-dig cyclization, thus providing a quick access to structurally complex pyrrole-fused heterocycles.
ABSTRACT
Direct electrosynthesis of hydrogen peroxide (H2O2) by oxygen reduction is a green and safe strategy to replace the traditional anthraquinone process. Herein, we have designed a two-dimensional redox-active cationic covalent triazine network to be used directly as a cost-effective metal-free electrocatalyst for the oxygen reduction reaction (ORR) to form H2O2. Such a dicationic 2D polymer possesses a porous structure with pore diameters of 2-10 nm and a total N content of 13.3 wt%. The electron paramagnetic resonance experiment confirms the reduction of a viologen-based polymer to radical cations and the subsequent generation of superoxygen radicals. The radical characteristics and high N content within this polymer are the essential for the efficient ORR via a two-electron pathway. As a result, the present electrocatalyst exhibits a high ORR activity and excellent H2O2 selectivity (â¼85%), thus providing a feasible possibility of designing highly selective metal-free electrocatalysts for electrocatalytic production of H2O2 from O2.